rs114387211

Variant names:

• chr7-30655713-T-C
• rs114387211
• NM_001883.5:c.920A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001883.5(CRHR2):​c.920A>G​(p.Lys307Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000259 in 1,613,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: CRHR2 NM_001883.5 missense, splice_region
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.99
• Publications: 2 publications found

Genes affected

CRHR2 (HGNC:2358): (corticotropin releasing hormone receptor 2) The protein encoded by this gene belongs to the G-protein coupled receptor 2 family, and the subfamily of corticotropin releasing hormone receptor. This receptor shows high affinity for corticotropin releasing hormone (CRH), and also binds CRH-related peptides such as urocortin. CRH is synthesized in the hypothalamus, and plays an important role in coordinating the endocrine, autonomic, and behavioral responses to stress and immune challenge. Studies in mice suggest that this receptor maybe involved in mediating cardiovascular homeostasis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jan 2011]

LOC124901609 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016458094).
• BP6: Variant 7-30655713-T-C is Benign according to our data. Variant chr7-30655713-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 726063.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001883.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	NM_001883.5	MANE Select	c.920A>G	p.Lys307Arg	missense splice_region	Exon 10 of 12	NP_001874.2
	CRHR2	NM_001202475.1		c.1001A>G	p.Lys334Arg	missense splice_region	Exon 11 of 13	NP_001189404.1	Q13324-2
	CRHR2	NM_001202482.2		c.917A>G	p.Lys306Arg	missense splice_region	Exon 10 of 12	NP_001189411.1	Q13324-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	ENST00000471646.6	TSL:1 MANE Select	c.920A>G	p.Lys307Arg	missense splice_region	Exon 10 of 12	ENSP00000418722.1	Q13324-1
	CRHR2	ENST00000348438.8	TSL:1	c.1001A>G	p.Lys334Arg	missense splice_region	Exon 11 of 13	ENSP00000340943.4	Q13324-2
	CRHR2	ENST00000506074.6	TSL:1	c.920A>G	p.Lys307Arg	missense splice_region	Exon 10 of 13	ENSP00000426498.3	Q13324-4

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 216 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000380 AC: 95 AN: 249956 AF XY: 0.000259

Gnomad AFR exome AF: 0.00554

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000138 AC: 202 AN: 1460910 Hom.: 0 Cov.: 33 AF XY: 0.000116 AC XY: 84 AN XY: 726778

African (AFR) AF: 0.00502 AC: 168 AN: 33476

American (AMR) AF: 0.000269 AC: 12 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26006

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111460

Other (OTH) AF: 0.000265 AC: 16 AN: 60358

GnomAD4 genome AF: 0.00142 AC: 216 AN: 152358 Hom.: 0 Cov.: 33 AF XY: 0.00141 AC XY: 105 AN XY: 74508

African (AFR) AF: 0.00491 AC: 204 AN: 41582

American (AMR) AF: 0.000588 AC: 9 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000564 Hom.: 2

Bravo AF: 0.00167

ESP6500AA AF: 0.00386 AC: 17

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000519 AC: 63

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.79	N
PhyloP100		8.0
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.032	D
Polyphen		1.0	D
Vest4		0.82
MVP		0.71
MPC		0.28
ClinPred		0.11	T
GERP RS		5.1
Varity_R		0.72
gMVP		0.73
Mutation Taster		=18/82	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs114387211; hg19: chr7-30695329;